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蛋白激酶Cβ抑制剂:糖尿病肾病及血管并发症的新治疗靶点。

Protein kinase C beta inhibitors: a new therapeutic target for diabetic nephropathy and vascular complications.

作者信息

Budhiraja S, Singh J

机构信息

Shiksha kunj Public School, Chinnot Colony, Rohtak-124001, Haryana, India.

出版信息

Fundam Clin Pharmacol. 2008 Jun;22(3):231-40. doi: 10.1111/j.1472-8206.2008.00583.x.

Abstract

Diabetic nephropathy (DN) has emerged as the major causative pathology in patients entering end-stage renal disease (ESRD) worldwide and it is responsible for 30-40% of all ESRD cases. Treatments for DN are centered on control of hyperglycemia and blood pressure control. However, current therapeutic regimens have not yet provided satisfactory prevention from the onset of DN. Protein kinase C (PKC) is an intracellular signaling molecule and activation of it plays an important role in the development of diabetic complications. In numerous experimental and clinical studies, inhibition of PKC (LY333531) has been shown to delay/halt the progression of diabetic complications. Presently, the drug is submitted in USA-FDA for new drug application in moderate to severe diabetic retinopathy. This review selectively discusses the role of PKC in DN and therapeutic effects produced by PKC inhibitors in DN. The role of PKC inhibitor in other diabetic complications is also discussed.

摘要

糖尿病肾病(DN)已成为全球进入终末期肾病(ESRD)患者的主要致病病理因素,占所有ESRD病例的30%-40%。DN的治疗主要集中在控制高血糖和血压。然而,目前的治疗方案尚未能令人满意地预防DN的发生。蛋白激酶C(PKC)是一种细胞内信号分子,其激活在糖尿病并发症的发生发展中起重要作用。在众多实验和临床研究中,抑制PKC(LY333531)已被证明可延缓/阻止糖尿病并发症的进展。目前,该药物已在美国向食品药品监督管理局(FDA)提交用于中重度糖尿病视网膜病变的新药申请。本综述选择性地讨论了PKC在DN中的作用以及PKC抑制剂在DN中产生的治疗效果。还讨论了PKC抑制剂在其他糖尿病并发症中的作用。

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